Frank, S. A. and Nowak, M. A. 2003. Developmental predisposition to cancer. Nature 422:494.
Many human cancers occur in renewing epithelial tissues, in which cellular lineages typically go through two distinct phases: early in life, cell populations expand exponentially to form the tissue, and for the remainder of life, the tissue is renewed by stem cells dividing to create an almost linear cellular history. Here we use a simple mathematical model to show that mutations that arise during the exponential phase probably seed tissues with stem cells carrying mutations that may predispose to cancer. Susceptibility to late-life cancers, such as those of the skin and colon, may therefore be influenced by somatic mutations that occur during early development.